ClinVar Miner

Submissions for variant NM_152703.5(SAMD9L):c.3374A>G (p.Gln1125Arg)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003003370 SCV003306871 uncertain significance not provided 2022-01-27 criteria provided, single submitter clinical testing In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available"). This variant has not been reported in the literature in individuals affected with SAMD9L-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 1125 of the SAMD9L protein (p.Gln1125Arg).
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV004786789 SCV005402311 likely pathogenic Ataxia-pancytopenia syndrome 2024-01-02 criteria provided, single submitter clinical testing The SAMD9L c.3374A>G (p.Gln1125Arg) missense change is absent in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). This variant has been identified in an individual with SAMD9L-related ataxia pancytopenia syndrome (Internal data). This individual presented additional somatic alterations that affect the SAMD9L gene, consistent with somatic rescue mechanism in response to deleterious germline mutations as previously described (PMID: 28202457, 29217778, 34621053). The in silico tool REVEL predicts a benign effect on protein function, but this prediction has not been confirmed by functional studies. In silico predictions have not been found to correlate with syndromic risk and are not considered supporting evidence of a pathogenic or benign effect (PMID: 34621053). In summary, this variant meets criteria to be classified as likely pathogenic.

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